Effects of Low Molecular Weight Heparin Versus Dabigatran on Platelet Aggregation in Patients With Stable Coronary Artery Disease

Effects of LMWH Versus Dabigatran on Platelet Aggregation in Patients With Stable Coronary Artery Disease

Anticoagulation with heparin is indicated in several situations, such as acute coronary disease (in combination with antiplatelet therapy) for the prevention and treatment of venous thromboembolism and situations with high risk of thromboembolism. Recently, the latest trials on anticoagulation for stroke prevention on atrial fibrillation have shown an increased risk for acute mycardial infarction on patients submitted to new oral anticoagulants, such as dabigatran. The mechanism is still unclear, however, in this context, some previous studies about interaction between anticoagulants ( mainly heparin) and platelet aggregation have shown conflicting results: while some suggest an inhibitory effect of heparin on platelet function, others suggest that heparin could promote an increase in platelet activation. The present study aims to assess the effects of the LMWH Enoxaparin and direct thrombin inhibitor, Dabigatran, on platelet aggregation, studied and compared by different methods in patients with chronic coronary artery disease (CAD).

Study Overview

• Status: Completed
• Conditions: Coronary Disease
• Intervention / Treatment: Drug: Dabigatran; Drug: Enoxaparin

Detailed Description

This is a prospective and open study. We will include 29 patients with chronic CAD, stable, using ASA. All patients will receive the same medications in effective doses recommended at each stage of the study, so that every individual is his self-control, the Enoxaparin will be administrated at a dose of 1mg/kg twice a day and Dabigatran at a dose of 150mg twice a day. Study Design: Phase 1 : There will be a first collection of blood samples from all patients at baseline for laboratory tests, then the patient will receive Dabigatran for 5 days and laboratory tests including platelet aggregation will be made, among others. After a 30 days washout period, enoxaparin will be administrated for 5 days and in the 6st day, the same laboratory tests, including platelet aggregation, will be performed.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • InCor Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age > 18 years old Coronary artery disease, defined as previous myocardial infarction and/or coronary angioplasty and/or Coronary Artery Bypass Graft (CABG) surgery and/or coronariography showing obstruction of at least 50 % in one of major epicardial vessels Treatment with Acetylsalicylic Acid (ASA) 100 mg/day

Exclusion Criteria:

Use in the last 7 days of oral anticoagulant or any other antiplatelet drug beside ASA Active bleeding Pregnancy or woman of childbearing age without contraceptive method Hemoglobin < 10 g/dL or hematocrit < 30 %, hematocrit > 50 %, platelets < 100.000/mm3 or > 500.000/mm3; creatinin clearance < 50 ml/minute Percutaneous coronary intervention (PCI) on the last 30 days before randomization (or PCI on the last year when drug-eluted stents are used); CABG surgery on the last 90 days; acute coronary syndrome on the last 60 days Active malignant neoplasm Active peptic ulcer disease on the last 60 days or upper gastrointestinal bleeding any time in life Refuse to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran; Dabigatran 150mg twice a day for five days	Drug: Dabigatran; Use for 5 days; Other Names: Pradaxa
Active Comparator: Enoxaparin; Enoxaparin 1mg/kg/day twice a day for five days	Drug: Enoxaparin; Use for 5 days; Other Names: Clexane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Platelet Aggregability	Comparing PLATELET AGGREGABILITY values through Multiplate test between patients on aspirin, assigned to the groups dabigatran and enoxaparin.	5 days after starting the drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Platelet Aggregability with other aggregability test	Comparing PLATELET AGGREGABILITY values through Verify Now test (units=ARU) between patients on aspirin assigned to the groups dabigatran and enoxaparin	5 days after starting the drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing the main outcome on pre-specified subgroups	elderly (age > 65 yrs-old) versus non-elderly male versus female smoking versus non-smoking patients diabetic versus non-diabetic	5 days after starting the drug
Correlate platelet aggregability and inflammation markers		5 days after starting the drug

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: José C Nicolau, PhD, InCor Heart Institute - University of São Paulo

Publications and helpful links

General Publications

• Arantes FBB, Menezes FR, Franci A, Barbosa CJDG, Dalcoquio TF, Nakashima CAK, Baracioli LM, Furtado RHM, Nomelini QSS, Ramires JAF, Kalil Filho R, Nicolau JC. Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial. Adv Ther. 2020 Jan;37(1):420-430. doi: 10.1007/s12325-019-01153-8. Epub 2019 Nov 22.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: December 4, 2014
• First Submitted That Met QC Criteria: March 10, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Estimate): April 29, 2016
• Last Update Submitted That Met QC Criteria: April 28, 2016
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: platelet function; dabigatran;enoxaparin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran; Enoxaparin
• Other Study ID Numbers: SDC 3877/13/002